Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

4H silicon carbide particle detectors: study of the defects induced by high energy neutron irradiation

During the last decade advances in the field of sensor design and improved base materials have pushed the radiation hardness of the current silicon detector technology to impressive performance. It should allow operation of the tracking systems of the Large Hadron Collider (LHC) experiments at nominal luminosity (1034 cm-2s-1) for about 10 years. The current silicon detectors are unable to cope with such an environment. Silicon carbide (SiC), which has recently been recognized as potentially radiation hard, is now studied. In this work it was analyzed the effect of high energy neutron irradiation on 4H-SiC particle detectors. Schottky and junction particle detectors were irradiated with 1 MeV neutrons up to fluence of 1016 cm-2. It is well known that the degradation of the detectors with irradiation, independently of the structure used for their realization, is caused by lattice defects, like creation of point-like defect, dopant deactivation and dead layer formation and that a crucial aspect for the understanding of the defect kinetics at a microscopic level is the correct identification of the crystal defects in terms of their electrical activity. In order to clarify the defect kinetic it were carried out a thermal transient spectroscopy (DLTS and PICTS) analysis of different samples irradiated at increasing fluences. The defect evolution was correlated with the transport properties of the irradiated detector, always comparing with the un-irradiated one. The charge collection efficiency degradation of Schottky detectors induced by neutron irradiation was related to the increasing concentration of defects as function of the neutron fluence.

Mg for hydrogen storage: synthesis, nanostructure and thermodynamics properties

Nowadays alternative energies are an extremely important topic and the possibility of using hydrogen as an energy carrier must be explored. Many problems infer the technological application of this abundant and powerful resource, one of them the possibility of storage. In the framework of suitable materials for hydrogen storage, magnesium has been the center of this study because it is cheap and the amount of stored hydrogen that it achieves (7.6 wt%) is extremely appealing. Nanostructure helps to overcome the slow hydrogen diffusion and the functionalization of surfaces with transition metals or oxides favors the hydrogen molecule dissociation/recombination. The aim of this research is the investigation of the metal-hydride transformation in magnesium nanoparticles synthesized by inert-gas condensation, exploiting the fact that they are a simple model system. The so produced nanostructured powder has been analyzed in response to nanoparticles surface functionalization by transition metal clusters, specifically palladium, nickel and titanium, chosen on the basis of their completely different Mg-related phase diagrams. The role of the intermetallic phases formed upon heating and hydrogenation treatments will be presented to provide a comprehensive picture of hydrogen sorption in this class of nanostructured storage materials.

Synthesis and characterization of new discotic polycyclic aromatic hydrocarbons and related pyrolytic nanostructures

Diskotische Hexa-peri-hexabenzocoronene (HBC) als molekulare, definierte graphitische Substrukturen sind bereits seit langem Gegenstand von Untersuchungen zu der Delokalisierung von π-Elektronen. In dieser Arbeit wurden zusätzlich Platin-Komplexe in das periphere Substitutionsmuster von HBC eingeführt. Dies führte zu einer Verbesserung der Emission von dem angeregten Triplett-Zustand in den Singulett-Grundzustand mit einer zusätzlichen Verlängerung der Lebensdauer des angeregten Zustandes. Zusätzlich erlaubte diese Konfiguration ein schnelles Intersystem-Crossing mittels einer verstärkten Spin-Orbit Kopplung, die sowohl bei tiefen Temperaturen, als auch bei Raumtemperatur exklusiv zu Phosphoreszenz (T1→S0) führte. Das Verständniss über solche Prozesse ist auch essentiell für die Entwicklung verbesserter opto-elektronischer Bauteile. Die Erstellung von exakt definierten molekularen Strukturen, die speziell für spezifische Interaktionen hergestellt wurden, machten eine Inkorporation von hydrophoben-hydrophilen, wasserstoffverbrückten oder elektrostatischen funktionalisierten Einheiten notwendig, um damit den supramolekularen Aufbau zu kontrollieren. Mit Imidazolium-Salzen funktionalisierte HBC Derivate wurden zu diesem Zwecke hergestellt. Eine interessante Eigenschaft dieser Moleküle ist ihre Amphiphilie. Dies gestattete die Untersuchung ihrer Eigenschaften in einem polaren Solvens und sowohl der Prozessierbarkeit als auch der Faserbildung auf Siliziumoxid-Trägern. Abhängig vom Lösungsmittel und der gewählten Konditionen konnten hochkristalline Fasern erhalten werden. Durch eine Substitution der HBCs mit langen, sterisch anspruchsvollen Seitenketten, konnte durch eine geeignete Prozessierung eine homöotrope Ausrichtung auf Substraten erreicht werden, was dieses Material interessant für photovoltaische Applikationen macht. Neuartige Polyphenylen-Metall-Komplexe mit diskotischen, linearen und dendritischen Geometrien wurden mittels einer einfachen Reaktion zwischen Co2(CO)8 und Ethinyl-Funktionalitäten in Dichlormethan hergestellt. Nach der Pyrolyse dieser Komplexe ergaben sich unterschiedliche Kohlenstoff-Nanopartikel, inklusive Nanoröhren, graphitischen Nanostäben und Kohlenstoff/Metall Hybrid Komplexe, die durch Elektronenmikroskopie untersucht wurden. Die resultierenden Strukturen waren dabei abhängig von der Zusammensetzung und Struktur der Ausgangssubstanzen. Anhand dieser Resultate ergeben sich diverse Möglichkeiten, um den Mechanismus, der zur Herstellung graphitischer Nanopartikel führt, besser zu verstehen.

Structural transformations related to organic solid-state reactions: correlation studies of NMR and X-ray analysis

Eine zielgerichtete Steuerung und Durchführung von organischen Festkörperreaktionen wird unter anderem durch genaue Kenntnis von Packungseffekten ermöglicht. Im Rahmen dieser Arbeit konnte durch den kombinierten Einsatz von Einkristallröntgenanalyse und hochauf-lösender Festkörper-NMR an ausgewählten Beispielen ein tieferes Verständnis und Einblicke in die Reaktionsmechanismen von organischen Festkörperreaktionen auf molekularer Ebene gewonnen werden. So konnten bei der topotaktischen [2+2] Photodimerisierung von Zimt-säure Intermediate isoliert und strukturell charakterisiert werden. Insbesondere anhand statischer Deuteronen- und 13C-CPMAS NMR Spektren konnten eindeutig dynamische Wasserstoffbrücken nachgewiesen werden, die transient die Zentrosymmetrie des Reaktions-produkts aufheben. Ein weiterer Nachweis gelang daraufhin mittels Hochtemperatur-Röntgen-untersuchung, sodass der scheinbare Widerspruch von NMR- und Röntgenuntersuchungen gelöst werden konnte. Eine Veresterung der Zimtsäure entfernt diese Wasserstoffbrücken und erhält somit die Zentrosymmetrie des Photodimers. Weiterhin werden Ansätze zur Strukturkontrolle in Festkörpern basierend auf der molekularen Erkennung des Hydroxyl-Pyridin (OH-N) Heterosynthon in Co-Kristallen beschrieben, wobei vor allem die Stabilität des Synthons in Gegenwart funktioneller Gruppen mit Möglichkeit zu kompetetiver Wasserstoffbrückenbildung festgestellt wurde. Durch Erweiterung dieses Ansatzes wurde die molekulare Spezifität des Hydroxyl-Pyridin (OH-N) Heterosynthons bei gleichzeitiger Co-Kristallisation mit mehreren Komponenten erfolgreich aufgezeigt. Am Beispiel der Co-Kristallisation von trans--1,2-bis(4-pyridyl)ethylen (bpe) mit Resorcinol (res) in Gegenwart von trans-1,2-bis(4-pyridyl)ethan (bpet) konnten Zwischenprodukte der Fest-körperreaktionen und neuartige Polymorphe isoliert werden, wobei eine lückenlose Aufklärung des Reaktionswegs mittels Röntgenanalyse gelang. Dabei zeigte sich, dass das Templat Resorcinol aus den Zielverbindungen entfernbar ist. Ferner gelang die Durchführung einer seltenen, nicht-idealen Einkristall-Einkristall-Umlagerung von trans--1,2-bis(4-pyridyl)ethylen (bpe) mit Resorcinol (res). In allen Fällen konnten die Fragen zur Struktur und Dynamik der untersuchten Verbindungen nur durch gemeinsame Nutzung von Röntgenanalyse und NMR-Spektroskopie bei vergleichbaren Temperaturen eindeutig und umfassend geklärt werden.

Photoinduced electronic transitions and leakage correlation to defects/dislocations in GaN heterostructures

III-nitride materials are very promising for high speed electronics/optical applications but still suffer in performance due to problems during high quality epitaxial growth, evolution of dislocation and defects, less understanding of fundamental physics of materials/processing of devices etc. This thesis mainly focus on GaN based heterostructures to understand the metal-semiconductor interface properties, 2DE(H)G influence on electrical and optical properties, and deep level states in GaN and InAlN, InGaN materials. The detailed electrical characterizations have been employed on Schottky diodes at GaN and InAl(Ga)N/GaN heterostructures in order to understand the metal-semiconductor interface related properties in these materials. I have observed the occurrence of Schottky barrier inhomogenity, role of dislocations in terms of leakage and creating electrically active defect states within energy gap of materials. Deep level transient spectroscopy method is employed on GaN, InAlN and InGaN materials and several defect levels have been observed related to majority and minority carriers. In fact, some defects have been found common in characteristics in ternary layers and GaN layer which indicates that those defect levels are from similar origin, most probably due to Ga/N vacancy in GaN/heterostructures. The role of structural defects, roughness has been extensively understood in terms of enhancing the reverse leakage current, suppressing the mobility in InAlN/AlN/GaN based high electron mobility transistor (HEMT) structures which are identified as key issues for GaN technology. Optical spectroscopy methods have been employed to understand materials quality, sub band and defect related transitions and compared with electrical characterizations. The observation of 2DEG sub band related absorption/emission in optical spectra have been identified and proposed for first time in nitride based polar heterostructures, which is well supported with simulation results. In addition, metal-semiconductor-metal (MSM)-InAl(Ga)N/GaN based photodetector structures have been fabricated and proposed for achieving high efficient optoelectronics devices in future.

Radiation-induced defects in calcium fluoride and their influence on material properties under 193 nm laser irradiation

Calcium fluoride (CaF2) is one of the key lens materials in deep-ultraviolet microlithography because of its transparency at 193 nm and its nearly perfect optical isotropy. Its physical and chemical properties make it applicable for lens fabrication. The key feature of CaF2 is its extreme laser stability. rnAfter exposing CaF2 to 193 nm laser irradiation at high fluences, a loss in optical performance is observed, which is related to radiation-induced defect structures in the material. The initial rapid damage process is well understood as the formation of radiation-induced point defects, however, after a long irradiation time of up to 2 months, permanent damage of the crystals is observed. Based on experimental results, these permanent radiation-induced defect structures are identified as metallic Ca colloids.rnThe properties of point defects in CaF2 and their stabilization in the crystal bulk are calculated with density functional theory (DFT). Because the stabilization of the point defects and the formation of metallic Ca colloids are diffusion-driven processes, the diffusion coefficients for the vacancy (F center) and the interstitial (H center) in CaF2 are determined with the nudged elastic band method. The optical properties of Ca colloids in CaF2 are obtained from Mie-theory, and their formation energy is determined.rnBased on experimental observations and the theoretical description of radiation-induced point defects and defect structures, a diffusion-based model for laser-induced material damage in CaF2 is proposed, which also includes a mechanism for annealing of laser damage. rn

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p > or = 0.05). We then used Affymetrix Genechip Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.

The Influence of PRP on Early Bone Formation in Membrane Protected Defects. A Histological and Histomorphometric Study in the Rabbit Calvaria

Platelet rich plasma (PRP) has been proposed to be a useful adjunct to bone grafting.

Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole or directly on the bone-forming cells. In addition, it is not known if the presentation of PTH by adding the amino acid sequence Arg-Gly-Asp (RGD) is essential for its osteopromotive effect. Local delivery of a bioactive substance at the right time and in the right concentration often constitutes a major challenge. Polyethylene glycol-based hydrogel (PEG) is a degradable vehicle developed for delivery of bioactive proteins. To enhance the mechanical stability of the PEG-bioactive substance complex, an osteoconductive bone substitute material is often needed.

Correction of erosion after suburethral sling insertion for stress incontinence: results and related sexual function

BACKGROUND: Suburethral slings are commonly used for the surgical treatment of female stress incontinence; occasionally they can cause erosion and dyspareunia. OBJECTIVES: The primary aim of this study is to determine the outcome after reclosure of the vaginal epithelium for suburethral sling erosion. Sexual function was assessed before and after intervention using the Female Sexual Function Index (FSFI) questionnaire. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective case-controlled study in which, between December 2005 and December 2007, we included patients who were referred to the Department of Urogynaecology because of vaginal erosion after suburethral sling insertion for urinary stress incontinence. For evaluation of sexual function, all patients filled in an FSFI questionnaire before intervention and at follow-up. All patients underwent gynaecological examination including colposcopy, and the site and size of the defect were noted. INTERVENTION: The edge of the vaginal epithelium was trimmed, mobilized, and closed with interrupted vertical Vicryl mattress sutures in a single layer. MEASUREMENTS: FSFI questionnaire and clinical findings. RESULTS AND LIMITATIONS: Twenty-one patients were included in the study. Eighteen patients with larger defects were operated on, and three defects healed after topical application of estrogen cream. In 16 patients, the defect had healed at follow-up; two patients with persisting defects were brought back to surgery and the procedure was repeated, paying particular attention to tension-free adaptation of vaginal tissue. In one patient, partial sling removal was performed after the second failed intervention. The domains of desire (p<0.0001), arousal (p<0.0003), lubrication (p<0.0001), satisfaction (p<0.0130), and pain (p<0.0001) improved significantly. Orgasm remained unchanged (p=0.4130; all two-tailed t-test). CONCLUSION: Suburethral erosion can be treated effectively by resuturing. Sexual function is improved in regard to desire, arousal, lubrication, satisfaction, and pain, but not orgasm. In septic patients and patients with a history of radiation, grossly infected tissue, or severe pain, excision of the mesh needs to be considered.

Up-regulation of the peroxiredoxin-6 related metabolism of reactive oxygen species in skeletal muscle of mice lacking neuronal nitric oxide synthase

Although neuronal nitric oxide synthase (nNOS) plays a substantial role in skeletal muscle physiology, nNOS-knockout mice manifest an only mild phenotypic malfunction in this tissue. To identify proteins that might be involved in adaptive responses in skeletal muscle of knockout mice lacking nNOS, 2D-PAGE with silver-staining and subsequent tandem mass spectrometry (LC-MS/MS) was performed using extracts of extensor digitorum longus muscle (EDL) derived from nNOS-knockout mice in comparison to C57Bl/6 control mice. Six proteins were significantly (P < or = 0.05) more highly expressed in EDL of nNOS-knockout mice than in that of C57 control mice, all of which are involved in the metabolism of reactive oxygen species (ROS). These included prohibitin (2.0-fold increase), peroxiredoxin-3 (1.9-fold increase), Cu(2+)/Zn(2+)-dependent superoxide dismutase (SOD; 1.9-fold increase), heat shock protein beta-1 (HSP25; 1.7-fold increase) and nucleoside diphosphate kinase B (2.6-fold increase). A significantly higher expression (4.1-fold increase) and a pI shift from 6.5 to 5.9 of peroxiredoxin-6 in the EDL of nNOS-knockout mice were confirmed by quantitative immunoblotting. The concentrations of the mRNA encoding five of these proteins (the exception being prohibitin) were likewise significantly (P < or = 0.05) higher in the EDL of nNOS-knockout mice. A higher intrinsic hydrogen peroxidase activity (P < or = 0.05) was demonstrated in EDL of nNOS-knockout mice than C57 control mice, which was related to the presence of peroxiredoxin-6. The treatment of mice with the chemical NOS inhibitor L-NAME for 3 days induced a significant 3.4-fold up-regulation of peroxiredoxin-6 in the EDL of C57 control mice (P < or = 0.05), but did not alter its expression in EDL of nNOS-knockout mice. ESR spectrometry demonstrated the levels of superoxide to be 2.5-times higher (P < or = 0.05) in EDL of nNOS-knockout mice than in C57 control mice while an in vitro assay based on the emission of 2,7-dichlorofluorescein fluorescence disclosed the concentration of ROS to be similar in both strains of mice. We suggest that the up-regulation of proteins that are implicated in the metabolism of ROS, particularly of peroxiredoxin-6, within skeletal muscles of nNOS-knockout mice functionally compensates for the absence of nNOS in scavenging of superoxide.

Crystal chemistry and hydrogen bonding of rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2 with variable OH, Cl, F

Three samples of the skarn mineral rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2, space group C2/c, a ≈7.6, b ≈ 18.5, c ≈ 15.5 Å, β ≈ 104°, with variable OH, Cl, F content were investigated by electron microprobe, single-crystal X-ray structure refinements, and Raman spectroscopy. “Rust1LCl” is a low chlorine rustumite Ca10(Si2O7)2(SiO4)(OH1.88F0.12)(Cl1.28,OH0.72) from skarns associated with the Rize batholith near Ikizedere, Turkey. “Rust2F” is a F-bearing rustumite Ca10(Si2O7)2(SiO4)(OH1.13F0.87) (Cl1 96OH0.04) from xenoliths in ignimbrites of the Upper Chegem Caldera, Northern Caucasus, Russia. “Rust3LClF” represents a low-Cl, F-bearing rustumite Ca10(Si2O7)2(SiO4)0.87(H4O4)0.13(OH1.01F0.99) (Cl1.00 OH1.00) from altered merwinite skarns of the Birkhin massif, Baikal Lake area, Eastern Siberia, Russia. Rustumite from Birkhin massif is characterized by a significant hydrogarnet-like or fluorine substitution at the apices of the orthosilicate group, leading to specific atomic displacements. The crystal structures including hydrogen positions have been refined from single-crystal X-ray data to R1 = 0.0205 (Rust1_LCl), R1 = 0.0295 (Rust2_F), and R1 = 0.0243 (Rust3_LCl_F), respectively. Depletion in Cl and replacement by OH is associated with smaller unit-cell dimensions. The substitution of OH by F leads to shorter hydrogen bonds O-H⋯F instead of O-H⋯OH. Raman spectra for all samples have been measured and confirm slight strengthening of the hydrogen bonds with uptake of F.This study discusses the complex crystal chemistry of the skarn mineral rustumite and may provide a wider understanding of the chemical reactions related to contact metamorphism of limestones.

Neural tube defects in Mexican-Americans living on the US-Mexico border: The effects of folic acid and dietary folate

Neural tube defects (NTDs) are malformations of the developing brain and spinal cord; the most common are anencephaly and spina bifida. Evidence from many populations suggests that 50% of NTDs can be prevented through daily consumption of folic acid. A recent study has reported that folic acid may not protect populations of Mexican descent. This finding has serious implications for women living along the US-Mexico border. Not only is risk high in these Mexican American women compared with other US women; they also differ markedly in supplemental folic acid and dietary folate consumption, and in NTD-related risks (e.g., obesity, diabetes). This case-control study investigated whether folic acid supplements and dietary folate reduces NTDs in Mexican Americans. Cases included liveborn, stillborn, electively and spontaneously aborted NTD-affected fetuses and infants occurring in the 14-county Texas-Mexico border. Controls were randomly selected from unaffected live births, frequency matched to cases by hospital and year. An in-person interview of 110 case and 113 control mothers solicited data on folic acid supplements, dietary folate, and other covariates. Consumption of folic acid-containing vitamins before conception was only 5% for both case and control women. Taking vitamins the trimester before conception had no apparent effect, after adjusting for covariates [odds ratio (OR) = 1.0, 95% confidence interval (CI) = 0.3–3.4]. Combining folate from vitamins and diet showed a 20% risk reduction for women consuming at least 400 μg of folate daily [OR = 0.8, 95% CI = 0.5–1.5]; however, this estimate is statistically indistinguishable from the null. Although consistent with an inherent ineffectiveness of supplemental folic acid, that so few women consumed multivitamins during the critical time severely limited the assessment of folic acid in this population. A reduced folate response in Mexican descent women may be due to a genetic heterogeneity for metabolizing folate. Alternatively, folate intakes may be insufficient to overcome other underlying risk factors. In conclusion, determining whether folic acid reduces NTD risk in Mexican American women requires further study in populations with higher folic acid exposures. Meanwhile, we should pursue all recommended prevention strategies to reduce risk, including motivating Mexican American women of childbearing age to take folic acid routinely. ^

Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.

BACKGROUND Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects. METHODS Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques. RESULTS Eosinophil extracellular trap formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating eosinophils. While the expression of both filaggrin and LEKTI was reduced, epithelial antimicrobial peptides (human beta-defensin-2, human beta-defensin-3, cathelicidin LL-37, psoriasin) and cytokines (TSLP, IL-25, IL-32, IL-33) were elevated in EoE as compared to normal esophageal tissues. There was a significant correlation between EET formation and TSLP expression (P = 0.02) as well as psoriasin expression (P = 0.016). On the other hand, a significant negative correlation was found between EET formation and LEKTI expression (P = 0.016). CONCLUSION Active EoE exhibits the presence of EETs. Indications of epithelial barrier defects in association with epithelial cytokines are also present which may have contributed to the activation of eosinophils. The formation of EETs could serve as a firewall against the invasion of pathogens.